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Background:

Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women.

Objective:

We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity.

Methods:

This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (${\text{fT}}_4$, ${\text{TT}}_4$) and triiodothyronine (${\text{fT}}_3$, ${\text{TT}}_3$), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores.

Results:

We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of ${\text{fT}}_4$, ${\text{TT}}_4$, ${\text{fT}}_3$, and ${\text{TT}}_3$ [absolute difference: $-0.62$; 95% confidence interval (CI): $-0.12$, $-0.01$; $p=0.04$; absolute difference: $-8.31$; 95% CI: $-13.8$, $-2.85$; $p=0.003$; absolute difference: $-0.37$; 95% CI: 0.54, $-0.19$; $p<0.0001$; and absolute difference: $-0.21$; 95% CI: $-0.32$, $-0.10$; $p=0.003$, respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb.

Conclusions:

Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740